tbuckley/cabot-search huggingface dataset:
Multiple Myeloma
Authors: Donald R. Korst, George O. Clifford, Willis M. Fowler, John Louis, John Will, Henry E. Wilson
Journal: JAMA (1964)

A COOPERATIVE STUDY of a treatment of myeloma by 21 institutions has been in progress for four years.<sup>1</sup>A uniform protocol, criteria, and data flow sheets have been followed and evaluated by the committee. Comparison survival data with previous forms of treatment was obtained in an ancillary myeloma study by the same cooperative group in the same institutions.<sup>2</sup>Cyclophosphamide (Cytoxan) was selected as an alkylating agent suitable for use in a low oral dose, longrange program. These results are based on a study of 165 patients who received the drug for at least 60 days (an "adequate trial"). Twenty percent (42) of the patients who started the study did not reach adequate trial status because of death (17), complications (8), or loss to follow-up (17). <h3>Materials and Methods</h3> Participating investigators placed on study as many patients as possible from their respective institutions. The diagnosis of multiple myeloma was
Health, Normality, and the Ghost of Gauss
Authors: Lila R. Elveback
Journal: JAMA (1970)

It has been suggested that "clinical normal values" can be estimated from routine laboratory records by purely statistical methods, so that accumulation of values for healthy persons is unnecessary. The basic premise for this view is that the routine laboratory values give a mixture of two gaussian (or "normal") distributions (one for the sick and one for the healthy) and that these can be identified. The results of the proposed method are compared with observed values for healthy persons tested in the same laboratories during the same period, and are found to be unsatisfactory. The distributions in healthy persons cannot be adequately described by a normal distribution. We propose that the misleading phrase "normal limits" be dropped, and that the phrase "clinical limits" be used to refer to the 2 1/2 and 97 1/2 percentage points of the distribution in healthy persons.
The Role of the Brain in Physical Disease
Authors: Redford B. Williams
Journal: JAMA (1990)

That the brain can exert profound effects on the body is by no means a new idea. The Bible contains an early description (Acts 5) of stress-induced sudden cardiac death: on being severely chastised by Peter for holding back part of a gift intended to support the early church, both Ananias and his wife Sapphira "fell down and gave up the ghost." In modern times such anecdotal reports have been supplemented by more systematic research, including, for example, laboratory studies documenting decreased myocardial perfusion during acute mental stress<sup>1</sup>and epidemiologic studies making the case that mental states are involved in the long-term development of coronary heart disease.<sup>2</sup> There is still skepticism, however, that mental states— and, hence, the brain—play an important role in physical illness, with some in positions of authority consigning such a notion to the realm of "folklore."<sup>3</sup>This skepticism stems in part from the
Hepatitis B and the HBsAg Carrier
Authors: Richard A. Wright
Journal: JAMA (1975)

Within six months, acute viral hepatitis, type B, developed in three individuals associated with a nursing home in Denver. This attack rate, 1.4 cases per 100 patients and employees, was apparently higher than the reported incidence of hepatitis B in Denver during the same period. Parenteral inoculations could not be implicated as the means of acquiring hepatitis B. However, two of the hepatitis patients had had sexual contact within six months before their illness with an employee who was an insulindependent diabetic and a symptomatic carrier of HB<sub>s</sub>Ag. In addition, anti-HB<sub>s</sub>antibodies were detected in his homosexual roommate. Although the chronic carrier was a food-handler, a seroepidemiologic survey of the employee population showed no spread of HB<sub>s</sub>Ag by means of food or casual contact. Only 1 (4.6%) of 22 employees tested had anti-HB<sub>s</sub>antibodies. These results suggest that household and, in particular, sexual contact with a symptomatic HB<sub>s</sub>Ag carrier may be an effective nonparenteral or inapparent parenteral mode of transmitting HB<sub>s</sub>Ag. (<i>JAMA</i>232:717-721, 1975)
Early Restrictive or Liberal Fluid Management for Sepsis-Induced Hypotension
Authors: Nathan I Shapiro, Ivor S Douglas, Roy G Brower, Samuel M Brown, Matthew C Exline, Adit A Ginde, Michelle N Gong, Colin K Grissom, Douglas Hayden, Catherine L Hough, Weixing Huang, Theodore J Iwashyna, Alan E Jones, Akram Khan, Poying Lai, Kathleen D Liu, Chadwick D Miller, Katherine Oldmixon, Pauline K Park, Todd W Rice, Nancy Ringwood, Matthew W Semler, Jay S Steingrub, Daniel Talmor, B Taylor Thompson, Donald M Yealy, Wesley H Self
Journal: New England Journal of Medicine (2023)

Intravenous fluids and vasopressor agents are commonly used in early resuscitation of patients with sepsis, but comparative data for prioritizing their delivery are limited.
Continued enteral nutrition until extubation compared with fasting before extubation in patients in the intensive care unit: an open-label, cluster-randomised, parallel-group, non-inferiority trial
Authors: Mickaël Landais, Mai-Anh Nay, Johann Auchabie, Noemie Hubert, Aurélien Frerou, Aihem Yehia, Alain Mercat, Maud Jonas, Frédéric Martino, Mikael Moriconi, Anne Courte, Vincent Robert-Edan, Alexandre Conia, Florent Bavozet, Pierre-Yves Egreteau, Cédric Bruel, Anne Renault, Olivier Huet, Marc Feller, Nicolas Chudeau, Martine Ferrandiere, Anne Rebion, Alain Robert, Bruno Giraudeau, Jean Reignier, Arnaud W Thille, Elsa Tavernier, Stephan Ehrmann, Satar MORTAZA, Julien DEMISELLE, Taoufik SASSI, Charles DELALE, Julien GROUILLE, Anne DE TINTENIAC, Marie GESLAIN, Herve FLOCH, Pierre BAILLY, Laetitia BODENES, Gwenaël PRAT, Pierre KALFON, Gaetan BADRE, Cecile JOURDAIN, Thierry MAZZONI, Anthony LE MEUR, Pierre Marie FAYOLLE, Anne HERON, Odile MAILLET, Nelly LEDOUX, Amélie ROLLE, Régine RICHARD, Marc VALETTE, Marie-Ange AZAIS, Caroline POUPLET, Konstantinos BACHOUMAS, Jean Christophe CALLAHAN, Christophe GUITTON, Cedric DARREAU, Montaine LEFEVRE, Guillaume LELOUP, Mélanie BERTEL, Jerome DAUVERGNE, Laurence PACAUD, Karim LAKHAL, Maelle MARTIN, Charlotte GARRET, Jean-Baptiste LASCARROU, Thierry BOULAIN, Armelle MATHONNET, Grégoire MULLER, François PHILIPPART, Marc TRAN, Julien FOURNIER, Jean-Pierre FRAT, Remi COUDROY, Delphine CHATELLIER, Guillaume HALLEY, Arnaud GACOUIN, Jerome HOFF, Servane VASTAL, Anne-Charlotte TELLIER, Mathilde BARBAZ, Charlotte SALMON GANDONNIERE, Emmanuelle MERCIER, Walid DARWICHE
Journal: The Lancet Respiratory Medicine (2023)
Effect of early mobilisation on long-term cognitive impairment in critical illness in the USA: a randomised controlled trial
Authors: Bhakti K Patel, Krysta S Wolfe, Shruti B Patel, Karen C Dugan, Cheryl L Esbrook, Amy J Pawlik, Megan Stulberg, Crystal Kemple, Megan Teele, Erin Zeleny, Donald Hedeker, Anne S Pohlman, Vineet M Arora, Jesse B Hall, John P Kress
Journal: The Lancet Respiratory Medicine (2023)
Effect of non-invasive ventilation after extubation in critically ill patients with obesity in France: a multicentre, unblinded, pragmatic randomised clinical trial
Authors: Audrey De Jong, Anne Bignon, François Stephan, Thomas Godet, Jean-Michel Constantin, Karim Asehnoune, Aude Sylvestre, Juliette Sautillet, Raiko Blondonnet, Martine Ferrandière, Philippe Seguin, Sigismond Lasocki, Amélie Rollé, Pierre-Marie Fayolle, Laurent Muller, Emmanuel Pardo, Nicolas Terzi, Séverin Ramin, Boris Jung, Paer-Selim Abback, Philippe Guerci, Benjamine Sarton, Hadrien Rozé, Claire Dupuis, Joel Cousson, Marion Faucher, Virginie Lemiale, Bernard Cholley, Gerald Chanques, Fouad Belafia, Helena Huguet, Emmanuel Futier, Elie Azoulay, Nicolas Molinari, Samir Jaber, AUDREY DE JONG, ANNE BIGNON, FRANÇOIS STEPHAN, THOMAS GODET, JEAN-MICHEL CONSTANTIN, KARIM ASEHNOUNE, AUDE SYLVESTRE, JULIETTE SAUTILLET, RAIKO BLONDONNET, MARTINE FERRANDIERE, PHILIPPE SEGUIN, SIGISMOND LASOCKI, AMELIE ROLLE, PIERRE-MARIE FAYOLLE, LAURENT MULLER, EMMANUEL PARDO, NICOLAS TERZI, SEVERIN RAMIN, BORIS JUNG, PAER-SELIM ABBACK, PHILIPPE GUERCI, BENJAMINE SARTON, HADRIEN ROZE, CLAIRE DUPUIS, JOEL COUSSON, MARION FAUCHER, VIRGINIE LEMIALE, BERNARD CHOLLEY, GERALD CHANQUES, FOUAD BELAFIA, HELENA HUGUET, EMMANUEL FUTIER, CLAUDINE GNIADEK, AURELIE VONARB, ALBERT PRADES, CARINE JAILLET, XAVIER CAPDEVILA, JONATHAN CHARBIT, THIBAUT GENTY, SAIDA REZAIGUIA-DELCLAUX, AUDREY IMBERT, CATHERINE PILORGE, ROMAN CALYPSO, ASTRID BOUTEAU-DURAND, MICHEL CARLES, HOSSEN MEHDAOUI, BERTRAND SOUWEINE, LAURE CALVET, MATTHIEU JABAUDON, BENJAMIN RIEU, CLARA CANDILLE, FLORIAN SIGAUD, BEATRICE RIU, LAURENT PAPAZIAN, SABINE VALERA, DJAMEL MOKART, LAURENT CHOW CHINE, MAGALI BISBAL, CAMILLE POULIQUEN, JEAN-MANUEL DE GUIBERT, MAXIME TOURRET, DAMIEN MALLET, MARC LEONE, LAURENT ZIELESKIEWICZ, JEANNE COSSIC, MONA ASSEFI, ELODIE BARON, CYRIL QUEMENEUR, ANTOINE MONSEL, MATTHIEU BIAIS, ALEXANDRE OUATTARA, ELINE BONNARDEL, SIMON MONZIOLS, MARTIN MAHUL, JEAN-YVES LEFRANT, CLAIRE ROGER, SABER BARBAR, FABIEN LAMBIOTTE, PIEHR SAINT-LEGER, CATHERINE PAUGAM, JULIEN POTTECHER, PIERRE-OLIVIER LUDES, LUCIE DARRIVERE, MARC GARNIER, ERIC KIPNIS, GILLES LEBUFFE, MATTHIAS GAROT, JEREMY FALCONE, BENJAMIN CHOUSTERMAN, MAGALI COLLET, ETIENNE GAYAT, JEAN DELLAMONICA, WILLY-SERGE MFAM, EVELINA OCHIN, MOHAMED NEBLI, NEJLA TILOUCHE, BENJAMIN MADEUX, DAVID BOUGON, YASSIR AARAB, FANNY GARNIER, ELIE AZOULAY, NICOLAS MOLINARI, SAMIR JABER
Journal: The Lancet Respiratory Medicine (2023)
Keratinocytes and immune cells in the epidermis are key drivers of inflammation in hidradenitis suppurativa providing a rationale for novel topical therapies
Authors: Stephanie L Schell, Zhaoyuan Cong, Mackenzie L Sennett, Samantha L Gettle, Amy L Longenecker, Stephanie R Goldberg, Joslyn S Kirby, Matthew F Helm, Amanda M Nelson
Journal: British Journal of Dermatology (2022)

Hidradenitis suppurativa (HS) is a debilitating inflammatory skin disease characterized by painful nodules, drainage and scarring in skin folds. Injectable adalimumab is the only drug approved by the US Food and Drug Administration for the treatment of HS. Although systemic Janus kinase (JAK) inhibitors show promise, serious side-effects have been reported. There are no highly effective topical treatments for HS; furthermore, the contribution of epidermal keratinocytes to the intense inflammation has largely been unexplored.We investigated the role of keratinocytes and epidermal immune cells in HS inflammation at all Hurley stages of disease severity. We aimed to determine whether ruxolitinib can mitigate inflammation from keratinocytes and to develop a better understanding of how topical therapeutics might benefit patients with HS.We used skin samples from 87 patients with HS (Hurley stages I-III) and 39 healthy controls to compare keratinocyte- and immune cell-driven epidermal inflammation, in addition to the response of lesional HS keratinocytes to treatment with interferon (IFN)-γ and ruxolitinib. We used haematoxylin and eosin staining, immunohistochemistry, immunoblotting and quantitative reverse-transcription polymerase chain reaction assessments in whole skin, isolated epidermis, and cultured keratinocytes from healthy controls and both nonlesional and lesional HS skin to identify and define epidermal and keratinocyte-mediated inflammation in HS and how this may be targeted by therapeutics.HS lesional keratinocytes autonomously secreted high levels of chemokines, such as CCL2, CCL3 and CXCL3, which recruited neutrophils, CD8 T cells, and natural killer cells to the epidermis. Keratinocytes were the dominant source of tumour necrosis factor-α and interleukin (IL)-6 in HS lesions with little to no contribution from underlying dermal immune cells. In the presence of IFN-γ, which is dependent on immune cell infiltrate in vivo, keratinocytes expressed increased levels of additional cytokines including IL-1β, IL-12, IL-23 and IL-36γ. The JAK inhibitor ruxolitinib mitigated the expression of inflammatory cytokines and chemokines in HS lesional keratinocytes, thus providing a rationale for future study as a topical treatment for HS.This study demonstrates that keratinocytes actively recruit immune cells to HS epidermis and interactions between these cells drive a broad inflammatory profile in HS epidermis. Targeting epidermal inflammation in HS with novel topical formulations may be highly efficacious with reduced systemic side-effects.
2 days versus 5 days of postoperative antibiotics for complex appendicitis: a pragmatic, open-label, multicentre, non-inferiority randomised trial
Authors: Elisabeth M L de Wijkerslooth, Evert-Jan G Boerma, Charles C van Rossem, Joost van Rosmalen, Coen I M Baeten, Frédérique H Beverdam, Johanna W A M Bosmans, Esther C J Consten, Jan Willem T Dekker, Marloes Emous, Anna A W van Geloven, Anton F Gijsen, Luc A Heijnen, An P Jairam, Damian C Melles, Augustinus P T van der Ploeg, Pascal Steenvoorde, Boudewijn R Toorenvliet, Maarten Vermaas, Bas Wiering, Bas P L Wijnhoven, Anne Loes van den Boom
Journal: The Lancet (2023)
Computational and artificial intelligence-based methods for antibody development
Authors: Jisun Kim, Matthew McFee, Qiao Fang, Osama Abdin, Philip M. Kim
Journal: Trends in Pharmacological Sciences (2023)

Due to their high target specificity and binding affinity, therapeutic antibodies are currently the largest class of biotherapeutics. The traditional largely empirical antibody development process is, while mature and robust, cumbersome and has significant limitations. Substantial recent advances in computational and artificial intelligence (AI) technologies are now starting to overcome many of these limitations and are increasingly integrated into development pipelines. Here, we provide an overview of AI methods relevant for antibody development, including databases, computational predictors of antibody properties and structure, and computational antibody design methods with an emphasis on machine learning (ML) models, and the design of complementarity-determining region (CDR) loops, antibody structural components critical for binding.
Multicomponent strategy with decentralised molecular testing for tuberculosis in Uganda: a cost and cost-effectiveness analysis
Authors: Ryan R Thompson, Talemwa Nalugwa, Denis Oyuku, Austin Tucker, Mariam Nantale, Annet Nakaweesa, Johnson Musinguzi, Tania F Reza, Alexandra J Zimmer, Olivia Ferguson, Stavia Turyahabwe, Moses Joloba, Adithya Cattamanchi, Achilles Katamba, David W Dowdy, Hojoon Sohn
Journal: The Lancet Global Health (2023)

BackgroundDecentralised molecular testing for tuberculosis could reduce missed diagnoses and losses to follow-up in high-burden settings. The aim of this study was to evaluate the cost and cost-effectiveness of the Xpert Performance Evaluation for Linkage to Tuberculosis Care (XPEL-TB) study strategy, a multicomponent strategy including decentralised molecular testing for tuberculosis, in Uganda.MethodsWe conducted a costing and cost-effectiveness analysis nested in a pragmatic cluster-randomised trial of onsite (decentralised) versus hub-and-spoke (centralised) testing for tuberculosis with Xpert MTB/RIF Ultra (Xpert) in 20 community health centres in Uganda. We collected empirical data on the cost of the XPEL-TB strategy (decentralised Xpert testing, workflow redesign, and performance feedback) and routine tuberculosis testing (onsite smear microscopy with specimen transport for centralised Xpert testing) from the health system perspective. Time-and-motion studies were performed to estimate activity-based service costs. Cost-effectiveness was assessed as the incremental cost (2019 US$) per tuberculosis diagnosis and per 14-day treatment initiation.FindingsThe XPEL-TB study ran from Oct 22, 2018, to March 1, 2020. Effectiveness and cost-effectiveness outcomes were assessed from Dec 1, 2018, to Nov 30, 2019 and included 4867 women and 3139 men. On a per-test basis, the cost of decentralised ($20·46, range $17·85–25·72) and centralised ($18·20, range $16·58–24·25) Xpert testing was similar. However, decentralised testing resulted in more patients receiving appropriate Xpert testing, so the per-patient cost of decentralised testing was higher: $20·28 (range $17·68–25·48) versus $9·59 (range $7·62–14·34). The XPEL-TB strategy was estimated to cost $1332 (95% uncertainty range $763–5558) per incremental tuberculosis diagnosis and $687 ($501–1207) per incremental patient initiating tuberculosis treatment within 14 days. Cost-effectiveness was reduced in sites performing fewer than 150–250 tests annually.InterpretationThe XPEL-TB strategy facilitated higher rates of Xpert testing for tuberculosis at a similar per-test cost and modest incremental cost per tuberculosis diagnosis and treatment initiation. Decentralised Xpert testing, with appropriate implementation supports, should be scaled up to clinics with sufficient testing volume to support a single-module device.FundingThe National Heart, Lung, and Blood Institute.
The state of health in Pakistan and its provinces and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019
Authors: Assad Hafeez, William James Dangel, Samuel M Ostroff, Ayyaz Gul Kiani, Scott D Glenn, Jaffar Abbas, Muhammad Sohail Afzal, Saira Afzal, Sajjad Ahmad, Ali Ahmed, Haroon Ahmed, Liaqat Ali, Muhammad Ali, Zahid Ali, Muhammad Arshad, Tahira Ashraf, Zulfiqar A Bhutta, Sadia Bibi, Zahid A Butt, Jai K Das, Zehra Fadoo, Asif Hanif, Khezar Hayat, Ayesha Humayun, Khalid Iqbal, Usman Iqbal, Nauman Khalid, Ejaz Ahmad Khan, Muhammad Shahzeb Khan, Ahmad Azam Malik, Muhammad Naveed, Shumaila Naz, Robina Khan Niazi, Zahra Zahid Piracha, Umar Saeed, Muhammad Salman, Zainab Samad, Muhammad Arif Nadeem Saqib, Syed Mahboob Shah, Izza Shahid, Masood Ali Shaikh, Hina Shamshad, Kanwar Hamza Shuja, Muhammad Suleman, Anayat Ullah, Irfan Ullah, Saif Ullah, Sana Ullah, Yasir Waheed, Abdul Waris, Simon I Hay, Christopher J L Murray, Ali H Mokdad
Journal: The Lancet Global Health (2023)
Pregnancy outcomes and vaccine effectiveness during the period of omicron as the variant of concern, INTERCOVID-2022: a multinational, observational study
Authors: Jose Villar, Constanza P Soto Conti, Robert B Gunier, Shabina Ariff, Rachel Craik, Paolo I Cavoretto, Stephen Rauch, Serena Gandino, Ricardo Nieto, Adele Winsey, Camilla Menis, Gabriel B Rodriguez, Valeria Savasi, Niyazi Tug, Sonia Deantoni, Marta Fabre, Begoña Martinez de Tejada, Maria Jose Rodriguez-Sibaja, Stefania Livio, Raffaele Napolitano, Nerea Maiz, Helena Sobrero, Ashley Peterson, Philippe Deruelle, Carolina Giudice, Jagjit S Teji, Roberto A Casale, Laurent J Salomon, Federico Prefumo, Leila Cheikh Ismail, Michael G Gravett, Marynéa Vale, Valeria Hernández, Loïc Sentilhes, Sarah R Easter, Carola Capelli, Emily Marler, Daniela M Cáceres, Guadalupe Albornoz Crespo, Ernawati Ernawati, Michal Lipschuetz, Ken Takahashi, Carmen Vecchiarelli, Teresa Hubka, Satoru Ikenoue, Gabriela Tavchioska, Babagana Bako, Adejumoke I Ayede, Brenda Eskenazi, Jim G Thornton, Zulfiqar A Bhutta, Stephen H Kennedy, Aris T Papageorghiou
Journal: The Lancet (2023)
DeepFundus: A flow-cytometry-like image quality classifier for boosting the whole life cycle of medical artificial intelligence
Authors: Lixue Liu, Xiaohang Wu, Duoru Lin, Lanqin Zhao, Mingyuan Li, Dongyuan Yun, Zhenzhe Lin, Jianyu Pang, Longhui Li, Yuxuan Wu, Weiyi Lai, Wei Xiao, Yuanjun Shang, Weibo Feng, Xiao Tan, Qiang Li, Shenzhen Liu, Xinxin Lin, Jiaxin Sun, Yiqi Zhao, Ximei Yang, Qinying Ye, Yuesi Zhong, Xi Huang, Yuan He, Ziwei Fu, Yi Xiang, Li Zhang, Mingwei Zhao, Jinfeng Qu, Fan Xu, Peng Lu, Jianqiao Li, Fabao Xu, Wenbin Wei, Li Dong, Guangzheng Dai, Xingru He, Wentao Yan, Qiaolin Zhu, Linna Lu, Jiaying Zhang, Wei Zhou, Xiangda Meng, Shiying Li, Mei Shen, Qin Jiang, Nan Chen, Xingtao Zhou, Meiyan Li, Yan Wang, Haohan Zou, Hua Zhong, Wenyan Yang, Wulin Shou, Xingwu Zhong, Zhenduo Yang, Lin Ding, Yongcheng Hu, Gang Tan, Wanji He, Xin Zhao, Yuzhong Chen, Yizhi Liu, Haotian Lin
Journal: Cell Reports Medicine (2023)

Medical artificial intelligence (AI) has been moving from the research phase to clinical implementation. However, most AI-based models are mainly built using high-quality images preprocessed in the laboratory, which is not representative of real-world settings. This dataset bias proves a major driver of AI system dysfunction. Inspired by the design of flow cytometry, DeepFundus, a deep-learning-based fundus image classifier, is developed to provide automated and multidimensional image sorting to address this data quality gap. DeepFundus achieves areas under the receiver operating characteristic curves (AUCs) over 0.9 in image classification concerning overall quality, clinical quality factors, and structural quality analysis on both the internal test and national validation datasets. Additionally, DeepFundus can be integrated into both model development and clinical application of AI diagnostics to significantly enhance model performance for detecting multiple retinopathies. DeepFundus can be used to construct a data-driven paradigm for improving the entire life cycle of medical AI practice.
Phase 1, open-label, dose-escalation study on the safety, pharmacokinetics, and preliminary efficacy of intravenous Coxsackievirus A21 (V937), with or without pembrolizumab, in patients with advanced solid tumors
Authors: Charles M Rudin, Hardev S Pandha, Matthew Zibelman, Wallace L Akerley, Kevin J Harrington, Daphne Day, Andrew G Hill, Steven J O'Day, Timothy D Clay, Gavin M Wright, Ross R Jennens, David E Gerber, Jonathan E Rosenberg, Christy Ralph, David C Campbell, Brendan D Curti, Jaime R Merchan, Yixin Ren, Emmett V Schmidt, Lisa Guttman, Sumati Gupta
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background Oncolytic virus V937 showed activity and safety with intratumoral administration. This phase 1 study evaluated intravenous V937±pembrolizumab in patients with advanced solid tumors. Methods Patients had advanced non-small cell lung cancer (NSCLC), urothelial cancer, metastatic castration-resistant prostate cancer, or melanoma in part A (V937 monotherapy), and metastatic NSCLC or urothelial cancer in part B (V937+pembrolizumab). Prior immunotherapy was permitted &gt;28 days before study treatment. Patients received intravenous V937 on days 1, 3, and 5 (also on day 8 in part B) of the first 21-day cycle and on day 1 of subsequent cycles for eight cycles. Three ascending dose-escalation cohorts were studied. Dose-escalation proceeded if no dose-limiting toxicities (DLTs) occurred in cycle 1 of the previous cohort. In part B, patients also received pembrolizumab 200 mg every 3 weeks from day 8 for 2 years; dose-expansion occurred at the highest-dose cohort. Serial biopsies were performed. Results No DLTs occurred in parts A (n=18) or B (n=85). Grade 3–5 treatment-related adverse events (AEs) were not observed in part A and were experienced by 10 (12%) patients in part B. The most frequent treatment-related AEs (any grade) in part B were fatigue (36%), pruritus (18%), myalgia (14%), diarrhea (13%), pyrexia (13%), influenza-like illness (12%), and nausea (12%). At the highest tested dose, median intratumoral V937 concentrations were 117,631 copies/mL on day 8, cycle 1 in part A (n=6) and below the detection limit for most patients (86% (19/22)) on day 15, cycle 1 in part B. Objective response rates were 6% (part A), 9% in the NSCLC dose-expansion cohort (n=43), and 20% in the urothelial cancer dose-expansion cohort (n=35). Conclusions Intravenous V937+pembrolizumab had a manageable safety profile. Although V937 was detected in tumor tissue, in NSCLC and urothelial cancer, efficacy was not greater than that observed in previous studies with pembrolizumab monotherapy. Trial registration number NCT02043665 .